Autism-like behavior reversed in laboratory mice

The research highlighted the brain's surprising elasticity and ability to adapt(Credit: Rama)

MIT scientists have
successfully reversed autistic-like behavioral patterns in mice. The
study focused on a gene called Shank3, which is missing in 1 percent
of individuals suffering from autism, and is believed to be vital for the development of a healthy adult brain.

Autism is a term for a
group of disorders that arise from a diverse range of genetic causes
that work to prevent the brain from developing normally, often making
the simplest of social interactions incredibly difficult.
According to the US Centers for Disease Control and Prevention
(CDC), instances of autism have risen 10-fold over the space of 40
years, with roughly 1 in 68 American children currently thought to be on the
autistic spectrum.

The new MIT research
may lead to gene therapy treatment for some patients that could
alleviate certain behavioral defects synonymous with autism. Prior
to the study, the Shank3 protein was known to be located in the
brain's synapses, where it acts as a scaffold for other proteins,
organizing them and allowing them to work together to allow a neuron
to form a cohesive response to an incoming signal.

Scientists have
observed that mutations or deficiencies of Shank3 in the brain can
cause synaptic disruptions in mice, leading to some of the irregular
behavioral patterns linked to autism. Furthermore, researchers have
noted a lower quantity of dendritic spines in mice
suffering from a Shank3 deficiency, with the abnormality becoming
more pronounced in the striatum.

For the purposes of the
recent study, scientists genetically engineered mice with inactive
Shank3 genes. As the mice developed, they exhibited a number of
autism-like behaviors including an aversion to social situations,
compulsive and repetitive behavior, and anxiety.

Between two to four
months after birth, the team introduced a breast cancer drug known as
tamoxifen into the food of the mice, which had the effect of
reactivating the Shank3 in the rodents' synapses.

Soon after, the team
noticed alterations in the behavior of the mice, including an
absence of repetitive actions and an increase in socializing. Mice
that were introduced to the tamoxifen at an earlier stage also
appeared to display a reduction in anxiety and improved motor skills.

The results of the
study display a surprising level of elasticityon a cellular
level, with the brain proving to be capable of rewiring itself and
generating new dendritic spines.

The next step for the
team will be to discern at what point circuits in the brain relating
to anxiety and motor function become too damaged to respond to the
newly activated Shank3 proteins.

"Some circuits are
more plastic than others," states lead author of a paper on the
findings Guoping Feng, a professor of brain and cognitive sciences at
MIT. "Once we understand which circuits control each behavior and
understand what exactly changed at the structural level, we can study
what leads to these permanent defects, and how we can prevent them
from happening."